The mission of the Pharmacology & Experimental Therapeutics Section (PETS) of NCI's Pediatric Oncology Branch (POB) is to develop more effective treatments for children and young adults with refractory cancers and genetic tumor predisposition syndromes (GTPS). A particular focus is on rare tumors with unmet need. Promising novel agents are studied in early clinical trials that evaluate toxicities, activity, pharmacokinetics, and pharmacodynamics. By leveraging unique NIH resources, I have applied the principles of drug development for refractory cancers to neurofibromatosis type 1 (NF1)-related tumors and built the nation's largest comprehensive NF1 clinical trials program directed at plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumors (MPNST).